PMID- 36973419 OWN - NLM STAT- MEDLINE DCOM- 20230508 LR - 20230522 IS - 2058-5276 (Electronic) IS - 2058-5276 (Linking) VI - 8 IP - 5 DP - 2023 May TI - Monocyte-derived macrophages contain persistent latent HIV reservoirs. PG - 833-844 LID - 10.1038/s41564-023-01349-3 [doi] AB - The development of persistent cellular reservoirs of latent human immunodeficiency virus (HIV) is a critical obstacle to viral eradication since viral rebound takes place once anti-retroviral therapy (ART) is interrupted. Previous studies show that HIV persists in myeloid cells (monocytes and macrophages) in blood and tissues in virologically suppressed people with HIV (vsPWH). However, how myeloid cells contribute to the size of the HIV reservoir and what impact they have on rebound after treatment interruption remain unclear. Here we report the development of a human monocyte-derived macrophage quantitative viral outgrowth assay (MDM-QVOA) and highly sensitive T cell detection assays to confirm purity. We assess the frequency of latent HIV in monocytes using this assay in a longitudinal cohort of vsPWH (n = 10, 100% male, ART duration 5-14 yr) and find half of the participants showed latent HIV in monocytes. In some participants, these reservoirs could be detected over several years. Additionally, we assessed HIV genomes in monocytes from 30 vsPWH (27% male, ART duration 5-22 yr) utilizing a myeloid-adapted intact proviral DNA assay (IPDA) and demonstrate that intact genomes were present in 40% of the participants and higher total HIV DNA correlated with reactivatable latent reservoirs. The virus produced in the MDM-QVOA was capable of infecting bystander cells resulting in viral spread. These findings provide further evidence that myeloid cells meet the definition of a clinically relevant HIV reservoir and emphasize that myeloid reservoirs should be included in efforts towards an HIV cure. CI - (c) 2023. The Author(s). FAU - Veenhuis, Rebecca T AU - Veenhuis RT AUID- ORCID: 0000-0002-9899-6277 AD - Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Abreu, Celina M AU - Abreu CM AD - Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Costa, Pedro A G AU - Costa PAG AUID- ORCID: 0000-0001-8290-8167 AD - Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Ferreira, Edna A AU - Ferreira EA AD - Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Ratliff, Janaysha AU - Ratliff J AD - Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Pohlenz, Lily AU - Pohlenz L AD - Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Shirk, Erin N AU - Shirk EN AD - Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Rubin, Leah H AU - Rubin LH AUID- ORCID: 0000-0003-2749-6328 AD - Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Epidemiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Blankson, Joel N AU - Blankson JN AD - Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Gama, Lucio AU - Gama L AD - Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. AD - Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. FAU - Clements, Janice E AU - Clements JE AUID- ORCID: 0000-0002-3096-1457 AD - Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jclements@jhmi.edu. AD - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jclements@jhmi.edu. AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jclements@jhmi.edu. LA - eng GR - R01 AI140789/AI/NIAID NIH HHS/United States GR - P30 MH075673/MH/NIMH NIH HHS/United States GR - P01 AI131306/AI/NIAID NIH HHS/United States GR - P30 AI094189/AI/NIAID NIH HHS/United States GR - R01 DA050529/DA/NIDA NIH HHS/United States GR - R01 AI127142/AI/NIAID NIH HHS/United States GR - R01 MH113512/MH/NIMH NIH HHS/United States GR - R01 MH127981/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230327 PL - England TA - Nat Microbiol JT - Nature microbiology JID - 101674869 RN - 0 (Anti-Retroviral Agents) SB - IM MH - Animals MH - Male MH - Humans MH - Female MH - *HIV Infections/drug therapy MH - *Simian Acquired Immunodeficiency Syndrome MH - *Simian Immunodeficiency Virus/genetics MH - Anti-Retroviral Agents/therapeutic use MH - *HIV-1/genetics MH - Virus Latency MH - Macrophages PMC - PMC10159852 MID - NIHMS1891209 COIS- The authors declare no competing interests. EDAT- 2023/03/28 06:00 MHDA- 2023/05/08 10:17 PMCR- 2023/03/27 CRDT- 2023/03/27 23:23 PHST- 2022/04/26 00:00 [received] PHST- 2023/03/01 00:00 [accepted] PHST- 2023/05/08 10:17 [medline] PHST- 2023/03/28 06:00 [pubmed] PHST- 2023/03/27 23:23 [entrez] PHST- 2023/03/27 00:00 [pmc-release] AID - 10.1038/s41564-023-01349-3 [pii] AID - 1349 [pii] AID - 10.1038/s41564-023-01349-3 [doi] PST - ppublish SO - Nat Microbiol. 2023 May;8(5):833-844. doi: 10.1038/s41564-023-01349-3. Epub 2023 Mar 27.